Levodopa and Protein – What About It?

Levodopa and Protein – What About It?

Kathrynne Holden, MS, RD (retired)

levodopa molecule.

What is levodopa?

Levodopa is a precursor of dopamine. First discovered in fava beans in the early 1900s, today levodopa is a mainstay in Parkinson treatment. Why? By the middle of the 1900s, scientists realized that neurons in the brain produced dopamine, which then guided the body’s movements. Later they found that in some people these neurons were gradually dying off, leading to dopamine deficiency and Parkinson’s disease. They could give dopamine by mouth, but it could not cross the blood-brain barrier, so it was useless if swallowed.

By 1961, however, research showed that levodopa – a precursor to dopamine – could cross the blood-brain barrier. Once there, the brain converted the levodopa to dopamine, where it treated the symptoms of PD – tremor, slowed movement, poor balance, shuffling gait. All were improved by use of levodopa. A few years later, scientists developed a pill form of levodopa to treat PD and it was hailed as a miracle.

It was and still is, the standard medication used to treat PD. It improved movement, balance, and walking ability; it decreased tremor, allowing people to continue their work and hobbies.

However, there were significant problems. Researchers soon learned that:

– its effects didn’t last long
– it caused severe nausea
– combining levodopa and protein was a problem – breakdown products of protein competed with levodopa for absorption from the small intestine.

Carbidopa molecule

After more research, scientists developed two compounds, carbidopa and benserazide, that, when combined with the levodopa, “protected” it to a large extent from competition with protein. So, in the mid-1970s, the pill was combined with carbidopa (in the United States) and benserazide (in Europe and other countries).

Since that time, new formulations continue to improve levodopa’s effectiveness. Sinemet CR is an extended-release form that can be taken with meals. Stalevo has an added COMT inhibitor that helps it last longer. Rytary (an extended-release form), Duodopa (delivery via pump directly into the small intestine), and Parcopa (does not need to be taken with water, it dissolves on the tongue) are some of the newer forms.

For some people, though, the levodopa and protein combination still can be a problem, even with the newer forms. Not everyone is protein-sensitive, especially in the early stages of PD. But some people are very sensitive to protein from the beginning of levodopa use; and for others, protein becomes more of a problem in later stages of PD. Let’s take a look at why this happens.

What exactly is protein?

Foods rich in protein

Protein is a long strand of amino acids. Nine of these are called “essential amino acids.” They are essential for human life, because our liver cannot make them. Foods that contain the greatest amount of essential amino acids are animal foods – meat, poultry, fish, eggs, and dairy foods. These contain all the nine essential aminos needed for human life, and are called “complete protein.” Most plant foods contain some, but not all, of the essential aminos, and are called “incomplete protein.” However, combining different plant foods gives us complete protein. Eating a combination of legumes (beans, peas, lentils), grains, nuts and seeds will give us all the essential aminos needed for health.

Why is protein a concern for those using levodopa?

When we eat protein – meat, for example – the stomach grinds it up into tiny particles and sends it to the small intestine. Enzymes there break down the meat protein strands into their individual amino acids.

There are twenty standard amino acids.

Then, special carriers in the intestine attract the aminos and carry them across the intestinal wall to the bloodstream. There are different carriers for the different amino acids, and this is where the problem begins.

Levodopa is also broken down into individual molecules. The carriers for levodopa are the same as the carriers for the “large neutral amino acids” – leucine, isoleucine, valine, phenylalanine, tryptophan, tyrosine, methionine, histidine. The meat we ate contains a large number of these aminos, whereas a levodopa pill has a much smaller amount of levodopa molecules.

So, when you eat a hamburger at the same time as taking levodopa, the intestinal carriers receive an avalanche of large neutral aminos, but only a tiny amount of levodopa. The carriers can be swamped by all the aminos, so that the levodopa must wait its turn. And, because levodopa has a short lifespan, its useful life may be nearly over by the time it’s absorbed into the blood and arrives at the brain.

This is why the levodopa and protein combination can cause problems, and why many people need to take levodopa about 30 minutes before meals. It has a clear path through the stomach and out of the small intestine, before the aminos arrive.

Types of protein

Animal protein is often more of a concern than plant proteins, though not always. Each individual can be unusually sensitive to a particular protein. One person may be affected most by dark turkey meat, another by ham, another by beef, eggs or sausage.

There is one protein, however, that seems to block levodopa to a greater extent, and for a longer time than other types – milk protein.

Milk protein may block levodopa more severely than other proteins

Of all the people I’ve talked to in over twenty years of counseling, more people have named milk as the food that blocks levodopa absorption the most severely. Many say that if they have milk on their cereal in the morning, levodopa won’t work for the rest of the day. The protein in milk is especially rich in the large neutral amino acids, and this may be why it’s a greater concern.

What about the different kinds of milk?

Cows’ milk and milk from goats and sheep are the types of milk most often used. All three are high in large neutral aminos, although they have different proportions of each. It may be an individual matter whether one kind of milk affects a person more than another type.

Why are some people affected by protein more than others?

There is no perfect answer to this question. Some people are unaffected by any kind of protein, while others are sensitive to certain proteins, but not others. Still others have some degree of sensitivity to all kinds of protein. Why? We can only speculate. Perhaps some people have a higher number of intestinal carriers receptive to these aminos, and thus are not so sensitive to milk or other proteins blocking levodopa.

What’s the best way to manage levodopa and protein?

Many people experience nausea when they first start using levodopa. So at first, it’s best to take levodopa with food, either with a meal, or with some crackers and juice. Usually, our bodies adapt to the levodopa in a few weeks, and then most people can take their levodopa about 30 minutes before meals. If you find that protein in food doesn’t block levodopa, you can certainly take it with meals.

It’s also good to be aware, though, that PD can slow the movement – “peristalsis” – of the gastrointestinal tract. When the stomach’s peristalsis is slowed, food may remain there for an abnormally long time. A high-fat meal can take as long as four to six hours to exit the stomach. Any levodopa taken while the stomach is full of food will be unable to exit into the small intestine; the levodopa must wait until the stomach clears. This can cause “motor fluctuations” – periods of time when PD medications are not working. If this is the case, talk to your neurologist, or a dietitian who can help you plan lower-fat, smaller meals that clear the stomach quickly.

A last, scary, thought

One of the scariest questions I hear, over and over down through the years, is: “Can you give me a list of foods that contain protein so I can avoid them?”

Of course I could provide a list of foods with protein. But, because I’m a health professional, the answer must be ‘No.”

Such a list would be equivalent to a recipe for death. Protein is absolutely necessary for human life. Every day your body must build new cells – blood, skin, muscles (including the heart), hair, organs – and enzymes, such as the insulin you produce to store glucose from the food you eat.

You require about ½ gram of protein per pound (about 1 gram per kilogram) of body weight per day, to restore and repair these cells. Without protein, your body would begin to devour its own muscles and organs, a condition called “protein-energy malnutrition.”

Today’s medications are far improved over the early days of levodopa. Timing of levodopa and foods goes a long way toward eliminating or minimizing off times. If you have signs of gastroparesis (slowed stomach emptying), such as acid reflux, lack of appetite at normal meal times, feeling full after only a few bites of food, burping, or heartburn, ask your doctor to assess the possibility of gastroparesis, which can be treated.

You don’t need to overdo protein intake, which the western diet often does. You just need to eat enough protein to meet your daily needs, and time your levodopa so that it wins the race with protein to the small intestine.

If you have any questions or thoughts, put them in the “Comments” section on this page, and I’ll respond. I hope to hear from you.

Good for you for choosing exercise to fight PD! Yes, you definitely need ample protein, and whey protein is a good source. Be aware, though, that whey is a concentrated source of three of the amino acids that compete with levodopa for absorption, particularly leucine. While this stimulates muscle protein synthesis, it may interfere with your Sinemet absorption. I would experiment cautiously; it may be necessary to take the whey protein well apart from levodopa, depending on your personal sensitivity to protein. Let us know how it works for you!

You’re very welcome, Andrew; and good for you for taking note of foods vs levodopa absorption. Diet can make a tremendous difference in motor fluctuations / off time, and you’re doing exactly the right thing in keeping track.

Hi Lori, do you mean could protein be blocking absorption of mirtazapine and/or ropinerole? Protein should not have an effect on either medication. For restless leg, I would be certain the person has had complete testing for blood levels of iron; also would consider trying magnesium supplements if deficiency of Mg is a possibility.

Hi — There is no research that is specific to PD; but virgin coconut oil appears to be heart-protective, and in animal studies, was protective against stress, which is very common in PD. It is a medium-chain triglyceride, which is metabolized differently than other types of saturated fats, and can be used directly for energy; it may be somewhat protective against Alzheimer’s disease, although there isn’t enough research to make any strong conclusions. However, it has been used for centuries in tropical countries as both food and medicine, believed to have antibacterial, antiviral, antioxidant, and immunostimulating properties. Used in moderation, it should be a fine addition to the daily diet.

Hi Jane, this is a difficult situation for sure. First, has his neurologist discussed use of one of the longer-lasting forms of levodopa, such as Stalevo or Rytary? That would cut down on the number of times daily that he needed to take his levodopa, and make it easier to time his meals.

Another thing that helps some people is use of “Liquid Sinemet.” Dissolving the sinemet makes it take effect much, much faster than swallowing the pill, so that meals can be eaten sooner. For the instructions on making liquid Sinemet, go to: http://www.parkinson.org/pd-library/books/medications

You can order a copy of the booklet, or download the entire booklet as a pdf, or go to Appendix C page 73 and print out just the page with the “Formula for Liquid Sinemet.”

Next, is the question – why does he need to take levodopa so often? Certainly this does happen as PD advances; but his doctor should also rule out:

1) gastroparesis (slowed stomach emptying) which is very common in PD and makes food stay in the stomach longer than normal. This means that the next dose of levodopa cannot be absorbed, because it can’t pass by the food in the stomach. So motor complications occur, and the Sinemet is increased to compensate. But if gastroparesis is the problem, it can be managed by changing the diet.

2) Prolonged constipation is also very common in PD, and can block levodopa absorption. If constipation lasts more than 3 days, ask his doctor about a laxative, such as Miralax, to relieve it. He may then find that his medications are more effective.

Kathryn; I was actually ‘browsing’ your site when we had a patient who stated Rytary had gluten in it. I work at a Neurology clinic in Nashville Tennessee and we deal with Rytary alot. Never knew it had Gluten in it. My comment actually is that you have a person whom you communicate alot with ‘Michael’, who had stated that his Rytary was too expensive after Humana. I am wondering if he tried going to the MY RYTARY website and filling out the registration forms. We have all our patients do this and they can provide financial assistance to patients AFTER the insurance pays. BIG SAVINGS. The doctors office should have the forms to send to the manufacturer to get the process started. IMPAX is the manufacturer.

Tami, thanks so much for your comments. I have heard from a number of people that Rytary is too expensive for them. Thanks so much for the information on MY RYTARY, I will make sure everyone knows about this resource, it may make it possible for more people to obtain this useful medication.

I was not aware that Rytary contained gluten — I have seen the list of inactive ingredients, and it does not appear there. If you see the patient again, could you find out where s/he obtained the information? I would definitely like to know if this is indeed the case, as quite a few people have leaky gut or gluten sensitivity.

Thanks again for your very helpful comments, I hope to hear from you again! -Kathrynne

Personally I haven’t had a problem with Sinemet or carbolev and protien. But what I have discovered is that cannabis, be it an oil taken orally or smoked, it is far more effective than any prescribed medication at controlling the symptoms of PD

How long should one wait after or before eating protein if they are taking carbidopa/levodopa. i just started March 1st and the instructions read ‘do not take with high protein foods. so, what’s considered ‘high’? is it best to take it on an empty stomach?

Usually, if you take levodopa with plenty of water/liquid 30 minutes before a meal, that’s enough time for the levodopa to dissolve and clear the stomach into the small intestine before the meal enters the stomach. For most people a snack of 5-6 grams of protein won’t interfere with levodopa. But a meal that has 20+ grams protein usually will interfere. You have started Sinemet quite recently — do you experience any nausea? If so, take the Sinemet with meals for awhile, until your body adapts; then take about 30 minutes before meals. I hope this is helpful. Let me know if this did not fully answer your question.

Kathrynne,
I know that in the past you have recommended that PD patients eat nuts and dried beans to get some of their protein. Does that form of protein interact with levodopa?
I’ve been eating lots of nuts as snacks, along with lentil soup at some meals, and find that I have some motor fluctuations, although not as bad as when I eat animal protein at a meal. I also find that I am suffering from more frequent urination, particularly at night. I have read that nuts may increase urine production. Is that the case?
Thank you for continuing to be a resource for us PD patients.

Hi Kram,
Yes, I do recommend frequent use of dried beans for their fiber and minerals, and nuts (especially raw) for their rich vitamin E content, along with trace minerals.

Each person reacts to the various kinds of proteins differently, but for most people, milk protein has the worst effect upon levodopa absorption, followed by other animal proteins, and finally by plant proteins. It sounds like you are experiencing worse fluctuations with animal protein than plant proteins. But also, be sure you’re not eating nuts or lentil soup close to the timing of your levodopa; take the levodopa, then wait about 30 minutes before eating any kind of protein.

Regarding increased frequency of urination, I doubt that nuts would have that significant an effect. This I would discuss with your primary care physician, because some conditions, and some medications, can cause increased urination, and may need to be addressed. Let me know how you are doing, and what your doctor says. My very best to you. -Kathrynne

I was wondering if I can ask a question on behalf of my dad. He was recently diagnosed with PD and is taking Levodopa. One of the main issues we continue to have is my dad has syncope. This occurs mostly around when he is eating lunch or dinner. It happened again on Saturday night where he begins to pass out at the table (luckily my mom and I caught it in time). I cooked dinner (chicken, cauliflower rice and corn). Since this happens more often, I’m seeing a pattern because it seems to be centered around food and what foods he eats. Although he wasn’t wearing the compression socks, he did take his Parkinson’s medication and properly timed his meals. Could it be that he should eliminate carbs? For example, protein with only vegetables and no potatoes/rice or carb vegetables. We’d like to try and resolve this issue. Can you provide any recommendations or suggestions?

Is there anything we can do to help with this? We cannot seem to figure out why this continues to happen.

Erin, had he had syncope before he began taking levodopa? If not, then I would suspect that medication is a factor, because syncope is a possible side effect of levodopa.

If he has experienced syncope before diagnosis of PD, then it’s possible it could be a result of GI stimulation, wherein the blood flow to the digestive system is altered. Also, syncope can indicate an increased risk of Parkinson’s disease.

Could a particular food, such as carbohydrate, be the cause? That, too, is possible, but I would consult his doctor before making dietary changes, because he should also be checked for dehydration, hypotension, and other medical conditions.

Let me know if you have other questions, and also, let me know how your dad is doing. My very best wishes to you both. -Kathrynne

Kathryn – My husband began having stomach pain when he tried Rytary two years ago. Neupro causes the same problem and now his regular Sinemet CR can be a problem (he’s been taking the CR for 9 years). He takes Sinemet 4 times daily. The first dose is taken with a bite of something like banana and never gives him pain. The second dose, around 11am rarely gives him a problem. It appears that the pain comes from having the Sinemet stay in his stomach for a longer period of time because food is slow to be digested. Another factor is that the gastroenterologist put him on Dexilant for the stomach pain. Sometimes even drinking a glass of water during the night would cause pain. We’re trying to back him off the acid blockers and will try several other things like cabbage juice and something called Glutagenics. The acid blockers slow his digestion yet he can’t sleep if he’s in pain all night long. I’m thinking maybe 5 or 6 small meals and smoothies and green juices might be helpful. Have you come across this problem and do you have any suggestions?

Hi Karen,
It sounds as though your husband has gastroparesis (slowed stomach emptying) and/or acid reflux/heartburn, and these unfortunately are all too common among people with PD. In this case, your plan for numerous small meals and smoothies is very sound – the stomach can process a small meal sooner than a full meal; and liquids move through the stomach by force of gravity, needing no stomach effort to grind them up, so they exit more quickly also.

It would be good to use fat in moderation, as it takes longer to clear the stomach than protein or carbohydrate. Also, for gastroparesis, Swedish Bitters may help to stimulate nerve impulses and help with stomach emptying; it can help with acid reflux as well. Ginger may also help with gastroparesis. It sounds like his gastroenterologist knows not to prescribe Reglan for the gastroparesis, which can greatly exacerbate PD symptoms. Domperidone, from Canada (with a doctor’s prescription) can be used safely with PD to speed stomach emptying.

I would also inquire of his gastroenterologist about the possibility that he might have small intestine bacterial overgrowth (SIBO), as it can occur secondary to gastroparesis.

Glutagenics contains DGL, which can help with acid reflux, along with aloe for healing. I have no experience with it, but Metagenics products have generally gotten good approval from ConsumerLabs, an independent supplement testing company.

If he has been on Dexilant for very long, he could be deficient in vitamin B12; you could ask the doctor to test for B12 deficiency.

I hope this is helpful for your husband, let me know. I look forward to hearing from you.

I’ve started to research gastroparesis and we can try the bitters. The heavy stomach and very slow digestion started with the Dexilant.

We’ve had multiple tests done, working with the Ultra Wellness Center, in Lenox, MA. No SIBO and no B-12 deficiency yet, although he takes a B-12 supplement.

It looks like the best solution for his stomach pain and possible ulcer from Sinemet might be the natural remedies like Glutagenics, cabbage juice, more and smaller meals plus smoothies and green juices. Staying on prescription Prevacid (the current acid blocker) for this long may be creating more problems than it’s solving and we hesitate to return to the gastroenterologist where the answer will be more drugs.

Thank you again for your suggestions and for confirming smaller, more frequent meals/smoothies!

Karen, I’m so happy to know that SIBO is not a concern, nor B12 deficiency; it can be as worrying as the stomach pain. Your husband appears to be under very good and thorough care; the testing can be tedious but ruling out diseases is as important as treating them. If the Wellness Center has a registered dietitian, I am pretty certain s/he would agree with the small frequent meals, cabbage juice, smoothies approach, and most will agree with use of natural remedies like Glutagenics as well. Dietitians worry about B12 and iron deficiency with use of acid blockers and PPIs like Dexilant. Keep up your good work, and let me know how your husband is doing, or if you have other questions.

Hi Kathryn,
I have a few questions about protein and weight gain. I’m very happy that I found your website. Let me introduce myself. My name is Karina, and I’m from NYC. My mother, Rosina is 58 years old and was diagnosed with PD when she was 50 years (she is considered a young onset PD patient). She at first started to showing symptoms of stiffness, fatigue and slowness until 2014 when her Doctor decided she was ready for surgery named DBS Surgery. It took a while for her to have that surgery for personal and financial reason, but her doctor decided for her to start taking the extended capsule of levodopa named Rytary. Since she took that medicine, part of those beginning symptoms disappeared. However, she developed a side effect of that medicine, dyskinesia. She was already considered a dyskenetic person. Therefore, she started losing weight because of those involuntary movement. This lasted for about 2 years more until she got the DBS Surgery on January 2017. Since the, she is not dyskenetic anymore which is a good relief for her. However, her walk was still the same as well as her freezing of gait. Plus, she gain the weight back and more. That’s when I got concerned about her because beside I’m her caregiver, I’m woman who loves fitness and eat healthy. Sometimes for me is difficult to know what type of food i can give to my mother because I know protein plays a really good role on her. I take supplements which are very natural, but I’m not quite sure if I should give it to her. That’s why Im here because I would like to what would be the best diet for her condition considering she is overweighted. How much protein do you think she need to intake a day? can she take protein supplements? like shakes? By the way, she is 5’0 and weights 168 pounds now. I want her to feel more energetic, even thou she is very active. She cooks at times, she walks around my block and at the park. I hope you can help me.

Hi Karina,
You are asking very good questions, and I hope I can help a bit. I will post an article on weight gain following DBS surgery at the end of this post, it may help explain why your mother has changed her eating habits so much.

For weight loss, as well as support of the brain, the Mediterranean diet is excellent; it is rich in vegetables, fruits, legumes, fish, and whole grains, which nourish the brain and benefit the body as well. It is high in many fibers, which help with constipation and help feed the protective bacteria in the gut – the “microbiome.” It is also high in powerful antioxidants, which fight free radicals. Parkinson’s is a stressful condition, and stress generates free radicals, so antioxidants can be very protective. Turmeric is an especially good source of protective antioxidants and is under study for its possible benefits in PD. It can be used in cooking, or mixed into smoothies (use a few grinds of black pepper, to boost absorption of turmeric and its curcuminoids). For more on turmeric, see my post “Turmeric and Parkinson’s disease,” https://nutritionucanlivewith.com/turmeric-parkinsons-disease/

As for protein, she needs about ½ gram of protein per pound of body weight per day. At 168 pounds, that would be 84 grams. However, as she loses weight, that amount will need to decrease. Her ideal weight for her age would probably be around 120 – 130 pounds, and protein needs would then be 60 – 65 grams/day. If she is still taking Rytary, or using Sinemet, she should always take it 30 minutes before meals so it is well absorbed before she eats any protein.